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Bibak-Bejandi Z, Arabpour Z, Razavi A, Moghtader A, Shahjahan S, Alzein A, Kwon JE, Bibak-Bejandi R, Aly N, Djalilian A. Limbal stem cell deficiency approaches and limbal niche restoration. Indian J Ophthalmol 2025; 73:468-482. [PMID: 40146135 DOI: 10.4103/ijo.ijo_464_25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Accepted: 02/24/2025] [Indexed: 03/28/2025] Open
Abstract
Approaches to limbal stem cell deficiency remain challenging, especially in bilateral cases, where healthy limbal stem cells are not accessible. While living-related allogeneic and allogeneic limbal stem cell sources have been utilized, their dependence on immunosuppression and its associated side effects pose significant limitations. Mucosal and mesenchymal stem cells have shown potential for differentiation into limbal stem cells and promoting corneal healing, primarily when cultured on the amniotic membrane or fibrin. However, none can fully replicate the original limbus. Innovations in surgical techniques, such as simple oral mucosal transplantation and subconjunctival or intrastromal mesenchymal stem cell injections, are emerging approaches. For successful limbal regeneration, both appropriate cells and suitable scaffolds are essential. Recent studies on decellularized and acellularized limbus models have demonstrated the potential to provide a three-dimensional native structure for cell seeding, retention, and differentiation. Creating a thin, evenly decellularized scaffold is a critical step in ensuring proper corneo-limbal slope formation, facilitating cell migration to the ocular surface. Harvesting the limbus, decellularization, and cell seeding are the three main steps in limbal reconstruction. Recent studies focus on microkeratome-assisted limbal harvesting to create a thin, even, and 360-degree limbal graft. This technique helps form an attached corneo-limbal interface, facilitating limbal stem cell migration. In the second step, acellularization is performed to preserve the extracellular matrix as much as possible, maintaining hemostasis and supporting paracrine interactions. The final steps involve recellularization and transplantation onto the eye. We summarize various limbal decellularization methods, their outcomes, and their potential in limbal reconstruction. More clinical studies are needed to validate this phase of limbal deficiency treatment.
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Affiliation(s)
- Zahra Bibak-Bejandi
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Zohre Arabpour
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Alireza Razavi
- Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
- Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Moghtader
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Sumaiya Shahjahan
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Ahmad Alzein
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Jeonghyun Esther Kwon
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | | | - Nuran Aly
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Ali Djalilian
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
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Nair S, Vanathi M, Tandon R. Biological topicals in ocular surface disorders. Indian J Ophthalmol 2025; 73:496-507. [PMID: 40146137 DOI: 10.4103/ijo.ijo_482_25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Accepted: 03/03/2025] [Indexed: 03/28/2025] Open
Abstract
Topical biological agents represent a significant advancement in the treatment of ocular surface diseases, offering a regenerative and therapeutic approach beyond conventional therapies. These agents are derived from serum (autologous or allogeneic), platelets, amniotic membrane, and pooled intravenous immunoglobulin. Their efficacy stems from their rich composition of growth factors, cytokines, and anti-inflammatory molecules that promote tissue healing, reduce inflammation, and enhance corneal regeneration. Autologous serum eye drops, closely mimicking natural tears, have been widely utilized for conditions such as dry eye disease, neurotrophic keratopathy, and persistent epithelial defects. Similarly, platelet derivatives, including platelet-rich plasma (PRP) and platelet lysate (PL), have demonstrated accelerated wound healing and nerve regeneration benefits. Amniotic membrane extracts and human amniotic fluid eye drops share the anti-inflammatory and regenerative properties of the human amniotic membrane. Recent advancements have introduced the use of topical IVIG, which modulates immune responses in severe inflammatory dry eye conditions, such as ocular graft-versus-host disease. Despite these promising applications, challenges such as variability in preparation, storage limitations, and cost remain. Nevertheless, the future of topical biological agents is promising, with emerging recombinant therapies and personalized treatment approaches shaping modern ophthalmologic care. As research continues to expand, these agents are poised to become integral components in managing ocular surface disorders, improving patient outcomes, and reducing dependence on traditional therapies.
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Affiliation(s)
- Sridevi Nair
- Cornea, Cataract and Refractive Surgery Services, Dr R P Centre, All India Institute of Medical Sciences, New Delhi, India
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Suleman A, Aluyi-Osa G, Ashipa F, Spadea L, Gagliano C, D’Esposito F, Zeppieri M, Musa M. Autologous blood in the management of ocular surface disorders. World J Exp Med 2024; 14:96412. [PMID: 39713083 PMCID: PMC11551708 DOI: 10.5493/wjem.v14.i4.96412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 09/23/2024] [Accepted: 10/22/2024] [Indexed: 10/31/2024] Open
Abstract
Autologous blood therapy has emerged as a promising modality in managing ocular surface disorders. This review provides a comprehensive overview of the current literature regarding the use of autologous blood in ocular surface disorders, encompassing its physiological basis, clinical applications, techniques, challenges, and future perspectives. The ocular surface, comprising the cornea, conjunctiva, and tear film, plays a critical role in maintaining visual function, and its disruption can lead to various pathological conditions. With its rich composition of growth factors, cytokines, and other bioactive molecules, autologous blood offers therapeutic potential in promoting corneal wound healing, reducing inflammation, and improving tear film stability. Clinical studies have demonstrated the efficacy and safety of autologous blood therapy in diverse ocular surface disorders, including persistent epithelial defects, neurotrophic keratopathy, and dry eye disease. However, challenges such as variability in treatment response, adverse effects, and optimal patient selection remain areas of concern. Further research is needed to elucidate the underlying mechanisms of action, refine treatment protocols, and explore synergistic approaches with other therapeutic modalities. Despite these challenges, autologous blood therapy holds promise as a valuable adjunctive treatment option for ocular surface disorders, offering new avenues for improving patient outcomes and quality of life. This review examines the mechanisms underlying ocular surface disorders while discussing existing autologous blood-based therapies for managing these disorders. Current clinical trials are also summarized, and a comparison between autologous blood therapy and conventional eyedrops is attempted. Finally, safe techniques and protocols for autologous blood medicine are elucidated, and adverse effects and future perspectives of this novel therapy are reviewed.
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Affiliation(s)
- Ayuba Suleman
- Department of Ophthalmology, Africa Eye Laser Centre, Km 7, Benin 300105, Nigeria
| | - Gladness Aluyi-Osa
- Department of Ophthalmology, Africa Eye Laser Centre, Km 7, Benin 300105, Nigeria
| | | | - Leopoldo Spadea
- Eye Clinic, Policlinico Umberto I, “Sapienza” University of Rome, Rome 00142, Italy
| | - Caterina Gagliano
- Department of Medicine and Surgery, University of Enna “Kore”, Enna 94100, Italy
- Mediterranean Foundation “G.B. Morgagni”, Catania 95125, Italy
| | - Fabiana D’Esposito
- Imperial College Ophthalmic Research Group Unit, Imperial College, London NW1 5QH, United Kingdom
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
| | - Mutali Musa
- Department of Optometry, University of Benin, Benin 3000283, Nigeria
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Kiristioglu MO, Baykara M, Yavas O, Kupeli ZA, Ozyigit MO. The effect of platelet-rich plasma and sodium alginate hydrogel on corneal wound healing after corneal alkali burns in rats with computer-assisted anterior segment optical coherence tomography image analysis. Exp Eye Res 2024; 247:110044. [PMID: 39151772 DOI: 10.1016/j.exer.2024.110044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 05/27/2024] [Accepted: 08/13/2024] [Indexed: 08/19/2024]
Abstract
Our objective was to determine the effect of a semi-synthetic sodium alginate hydrogel and its combination with platelet-rich plasma (PRP) on histopathological, biochemical, clinical, and anterior segment optical coherence tomography (AS-OCT) data. Alkali chemical burn of the cornea was induced. Injured rats were randomly divided into five equal groups and topically treated with phosphate-buffered saline (sham), platelet-rich plasma (PRP), 0.5% sodium citrate, a semi-synthetic sodium alginate hydrogel, or a combination of PRP and hydrogel (combined group) three times daily. The degree of corneal opacity (CO), corneal epithelial staining (CES), percentage of corneal epithelial defects (CEDP), degree of ciliary hyperemia (CH), neovascularization size (NVS), and extent of neovascularization (NVE) were evaluated. AS-OCT was performed at nine days, and then rats were sacrificed. Histological examination and enzyme-linked immunosorbent assays were performed to detect the concentrations of IL-1β and MMP-9 in the cornea. There were no significant differences between the groups regarding CEDP, CO, CES, CH, NVS, or NVE on the first day after corneal alkali burn injury (p > 0,05). At the last examination, CO was significantly lower in the PRP group than in the sham group (p = 0,044), while the CO concentrations were similar in terms of NVS (p > 0,05). Similarly, in terms of tissue MMP-9 levels, there were no significant differences between groups (p > 0,05). However, there was a significant difference in tissue IL-1β levels between the groups (p < 0,001). In the PRP and combined groups, the level of IL-1β was significantly lower than that in the sham group (p = 0,043 and p = 0,036, respectively). There was a significant difference in epithelial necrosis between the PRP, and it was the lowest in the combined group (p = 0,003). Epithelial thickness was highest in the combined group (p = 0,002). CEDP was significantly different at the last visit between the groups (p = 0.042). The fastest epithelial closing rate was observed for the combined group (p = 0,026). There was a significant negative correlation between tissue MMP-9 levels and corneal solidity and between tissue MMP-9 levels and the corneal area according to the AS-OCT measurements (p = 0,012 and p = 0,027, respectively). When used alone, topical hydrogel application did not significantly enhance the healing of corneal wounds. However, when combined with PRP, it leads to an increased rate of epithelial closure and neovascularization. This combination did not exacerbate inflammation or corneal opacity compared to PRP alone. The anticoagulant citrate solution in the PRP tube did not prove effective. The synergistic use of PRP and hydrogel could enhance epithelial thickness and reduce epithelial necrosis. The use of new parameters for corneal wound healing assessment was facilitated through AS-OCT image processing.
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Affiliation(s)
| | - Mehmet Baykara
- Department of Ophthalmology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Ozkan Yavas
- Department of Veterinary Pathology, Bursa Uludag University Faculty of Veterinary Medicine, Bursa, Turkey
| | - Zehra Avci Kupeli
- Department of Veterinary Pathology, Bursa Uludag University Faculty of Veterinary Medicine, Bursa, Turkey
| | - Musa Ozgur Ozyigit
- Department of Veterinary Pathology, Bursa Uludag University Faculty of Veterinary Medicine, Bursa, Turkey
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Bian Y, Jurkunas U. Ocular Chemical Injuries and Limbal Stem Cell Deficiency (LSCD): An Update on Management. Int Ophthalmol Clin 2024; 64:31-48. [PMID: 38525980 DOI: 10.1097/iio.0000000000000487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2024]
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Çınar H, Temizsoylu MD, İpek V. Comparative evaluation of platelet-rich plasma, autologous blood serum, and umbilical cord serum for corneal healing after penetrating keratoplasty in New Zealand rabbits. Exp Eye Res 2024; 240:109779. [PMID: 38176514 DOI: 10.1016/j.exer.2023.109779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 11/24/2023] [Accepted: 12/31/2023] [Indexed: 01/06/2024]
Abstract
This study aimed to evaluate the effects of platelet-rich plasma (PRP), autologous blood serum (ABS), and umbilical cord serum (UCS) on corneal healing following penetrating keratoplasty (PK). A total of 120 New Zealand white rabbits, forty were designated as donors, while the remaining eighty rabbits were randomly divided into four groups after undergoing PRP Group (n = 20), ABS Group (n = 20), UCS Group (n = 20) and Control Group (n = 20). Corneal opacity score, corneal vascularization, corneal staining, histopathological analysis, and immunohistochemical analysis (including CD4+, CD8+, and major histocompatibility complex [MHC] II) were assessed at postoperative 1, 2, 3, and 12 weeks. The results showed that corneal opacity score and corneal vascularization did not differ significantly among the groups. However, corneal staining was found to be statistically higher in the PRP group (0.40 ± 0.60) compared to the other groups (p = 0.011). Immunohistochemical examination revealed no significant differences in CD4+, CD8+, and MHC II levels among the groups. Notably, in all groups, CD4+, CD8+, and MHC II levels were significantly higher at 12 weeks compared to other time points. PRP, ABS, and UCS demonstrated positive effects on corneal healing after PK. However, among the three products, PRP exhibited a superior healing effect compared to ABS and UCS crucial in the postoperative period following PK procedures, as they significantly impact visual quality, graft transparency, graft survival, and prevention of stromal resorption caused by infections. Despite the avascular nature of the cornea and its immune privilege, failure to resolve epithelial defects (ED) commonly observed after PK can result in irreversible scarring and ulceration, leading to graft rejection. While epithelial defects are observed in 14-100% of cases on the first postoperative day, approximately 3-7% of them persist as non-healing ED in subsequent periods. In conclusion, our study demonstrated that PRP, ABS, and UCS have a positive effect on corneal healing after PK.
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Affiliation(s)
- Harun Çınar
- Department of Surgery, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur, Turkey.
| | - Mustafa Doğa Temizsoylu
- Department of Surgery, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur, Turkey
| | - Volkan İpek
- Department of Patology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur, Turkey
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Kwaku Akowuah P, Junior Obinwanne C, Owusu E, Kyeremeh S, Bonsu K, Karikari LAA, Akyaa Akomeah F, Kyei Nkansah E, Kobia-Acquah E. Platelet-rich plasma for treating dry eye disease - A systematic review and meta-analysis. Cont Lens Anterior Eye 2024; 47:102091. [PMID: 37951738 DOI: 10.1016/j.clae.2023.102091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 10/20/2023] [Accepted: 11/04/2023] [Indexed: 11/14/2023]
Abstract
PURPOSE Dry eye disease has public health and economic significance. Platelet-rich plasma is rich in anti-inflammatory agents and growth factors, both beneficial for ocular surface repair. This study aimed to conduct a systematic review and meta-analysis to summarize the benefits of platelet-rich plasma for treating dry eye disease and its adverse effects. METHODS Prospective comparative studies using platelet-rich plasma as monotherapy for dry eye disease were included for efficacy assessment. Before-after studies were included for adverse events assessment. Data sources included PubMed, Google Scholar, Web of Science, and Scopus. A systematic review and meta-analysis protocol was pre-registered on PROSPERO (CRD42022347982). PRISMA guidelines were followed. The National Health Institute (NIH) quality assessment tool for before-after studies, the Cochrane risk of bias tool (RoB2), and the methodological index for non-randomized studies were used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. RESULTS 19 studies (10 comparative and 9 before-after) were included in the systematic review and meta-analysis. The occurrence rate of adverse effects was 2.6 % (95 % CI: 0.5 - 4.7). The pooled standardized mean difference (SMD) for dry eye symptoms was 0.81 (95 % CI: 0.25 - 1.37; I2 = 82 %; p < 0.00001; Z = 2.84, p = 0.004); tear quality was 0.44 (95 % CI: 0.06 - 0.81; I2 = 67 %; p = 0.003; Z = 2.26, p = 0.02); tear quantity was 0.45 (95 % CI: 0.03 - 0.88; I2 = 74 %; p = 0.0003; Z = 2.10, p = 0.04); and corneal staining 0.72 (95 % CI: 0.14 - 1.30; I2 = 85 %; p < 0.00001; Z = 2.43, p = 0.02). CONCLUSION The current study shows that platelet-rich plasma is efficacious in managing dry eye disease, significantly reducing dry eye signs and symptoms. Such significant improvements could translate to improved quality of life.
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Affiliation(s)
| | | | - Ebenezer Owusu
- College of Optometry, University of Houston, Houston, TX, USA.
| | - Sylvester Kyeremeh
- Department of Optometry and Visual Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Kwaku Bonsu
- College of Optometry, University of Houston, Houston, TX, USA.
| | | | - Felicia Akyaa Akomeah
- Department of Optometry and Visual Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | - Ernest Kyei Nkansah
- Centre for Eye Research Ireland, Environmental Sustainability and Health Institute, Technological University Dublin, Dublin, Ireland
| | - Emmanuel Kobia-Acquah
- Department of Optometry and Visual Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; Centre for Eye Research Ireland, Environmental Sustainability and Health Institute, Technological University Dublin, Dublin, Ireland.
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Shome S, Kodieswaran M, Dadheech R, Chevella M, Sensharma S, Awasthi S, Bandyopadhyay A, Mandal BB. Recent advances in platelet-rich plasma and its derivatives: therapeutic agents for tissue engineering and regenerative medicine. PROGRESS IN BIOMEDICAL ENGINEERING (BRISTOL, ENGLAND) 2024; 6:012004. [PMID: 39655847 DOI: 10.1088/2516-1091/ad1338] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 12/07/2023] [Indexed: 12/18/2024]
Abstract
Platelet rich plasma (PRP) is a suspension of bioactive factors and chemokine enriched plasma. Platelets are a distinctive source of membrane bound and soluble proteins that are released upon their activation. The higher count of platelets renders PRP with an array of tissue regenerative abilities. PRP can be employed in the form of platelet containing plasma, platelet lysate plasma, or in the form of a pre-gelled fibrin matrix. PRP has been an essential alternative source of growth factors in the healing and regeneration of various tissues, such as musculoskeletal, cardiovascular, and dermal tissue, with additional applications in other tissues, such as hepatic and neural. A wide range of preparative and isolation strategies have been developed for various forms of PRP at laboratory and commercial scales. Concomitantly, PRP has found its applicability as an active component in several tissue regenerative approaches, including 3D printed/bioprinted constructs, injectable hydrogels, and crosslinked scaffolds. This review focuses on the various forms of PRP and their preparation methods, the latest tissue engineering applications of PRP, and the various tissue-specific clinical trials and findings conducted using PRP. We have further discussed the optimizations required in the methods of preparation, delivery, and long-term storage of PRP. Therefore, this review seeks to benefit the scope of research on PRP-based therapeutic agents in tissue engineering by providing comprehensive insights into the widespread application. We envisage PRP could be instrumental in future patient-specific tissue engineering applications in both pre-clinical and clinical settings.
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Affiliation(s)
- Sayanti Shome
- Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - M Kodieswaran
- Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Rajat Dadheech
- Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Maheshwari Chevella
- Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Sreemoyee Sensharma
- Jyoti and Bhupat Mehta School of Health Sciences and Technology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Sanu Awasthi
- Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Ashutosh Bandyopadhyay
- Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Biman B Mandal
- Biomaterials and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
- Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
- Jyoti and Bhupat Mehta School of Health Sciences and Technology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
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Hassan A, Telandro A, Barguigua A, Baba M, Körber N. Evaluation of the Use of Highly Concentrated Autologous Platelet-Rich Plasma and Platelet-Rich Fibrin Membrane to Improve the Outcome in the Management of Severe Dry Eye Disease, Corneal Neurotrophic Ulcer and Corneal Burn. Cureus 2024; 16:e51794. [PMID: 38322082 PMCID: PMC10846557 DOI: 10.7759/cureus.51794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/07/2024] [Indexed: 02/08/2024] Open
Abstract
INTRODUCTION The aim of this study was to evaluate the use of highly concentrated platelet-rich plasma (PRP) subconjunctival injections, in combination with eye drops (eye PRP, or E-PRP), in treating dry eye disease (DED) and the use of platelet-rich fibrin (PRF) membrane in treating corneal burns and neurotrophic ulcers for the restoration of the homeostasis of the tear film and the morphology and function of the cornea. METHODS We studied 16 patients (n=32 eyes) with severe DED. The disease was graded as severe according to the Oxford Grading Scale. There were 12 males (75%) and four females (25%) with a mean age of 56 years; these patients were treated with monotherapy, which involved a single subconjunctival injection of 0.2-0.3 mL of PRP prepared from autologous blood, followed by application of autologous PRP eye drops four times a day for 15 days between September 2019 and December 2020 in the same geographic area. All patients gave written informed consent before undergoing the outlined treatment protocol. We evaluated best corrected visual acuity (BCVA), Schirmer test score, tear film breakup time (TBUT) and corneal staining with fluorescein (Oxford Grading Scale) before and after six to eight weeks of treatment. Subjective normalization was defined by a decrease in the Ocular Surface Disease Index (OSDI) score to 10 or less, an objective normalization of the TBUT to five to six seconds, improvement in the Schirmer test score and Oxford grading and the BCVA gain of at least one line in the vision chart (Snellen chart). Furthermore, we report on the results from different variants of platelet concentrate-based treatments in five cases of corneal diseases: neurotrophic ulcers and corneal burns due to different causes (e.g., chemical burns) using E-PRP and PRF membrane with regard to normalization of morphology and function. RESULTS The OSDI score decreased to normalization in 75% of the patients (p=6.545 × 10-15). TBUT was restored significantly in 20 of 32 eyes from 2.78±0.55 to 5.43±0.71 (p=1.612 × 10-24). The Schirmer test score showed an improvement from 4.46±0.67 to 10.28±1.18 (p=3.411 × 10-29), and BCVA improved by 43.75%, from 0.15±0.19 to 0.09±0.16 (logMAR, p=0.2331). Oxford grading changed to Scale I in 75% and Scale 0 in 25% of the patients. No complications or adverse reactions occurred in the five cases of corneal injuries. We observed a restoration of the morphology and function of the cornea with PRP injections or PRF+PRP application in 7-12 days, depending on the severity of the initial finding. CONCLUSION PRP treatment is a new approach in ophthalmology with impressive results. Although patients show good compliance and acceptance of the treatment protocol, studies with larger sample sizes are needed to confirm and optimize its use.
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Affiliation(s)
| | - Alain Telandro
- Ophthalmology, Ophtalmologue Le Cannet-des-Maures, Cannes, FRA
| | - Abouddihaj Barguigua
- Microbiology, Polydisciplinary Faculty, Sultan Moulay Slimane University, Beni Mellal, MAR
| | - Mustafa Baba
- Environment and Climate, Ecole Hassania des Travaux Publics, Casablanca, MAR
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Razavi MS, Ebrahimnejad P, Javar HA, Weppelmann TA, Akbari J, Amoli FA, Atyabi F, Dinarvand R. Development of dual-functional core-shell electrospun mats with controlled release of anti-inflammatory and anti-bacterial agents for the treatment of corneal alkali burn injuries. BIOMATERIALS ADVANCES 2023; 154:213648. [PMID: 37812983 DOI: 10.1016/j.bioadv.2023.213648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 09/19/2023] [Accepted: 09/30/2023] [Indexed: 10/11/2023]
Abstract
In this study, a novel dual-drug carrier for the co-administration of an anti-inflammatory and antibiotic agent consisting of core-shell nanofibers for the treatment of cornea alkali burns was designed. The core-shell nanofibers were prepared via coaxial electrospinning of curcumin-loaded silk fibroin as the core and vancomycin-loaded chitosan/polyvinyl alcohol (PVA) as the shell. Electron microscopy (SEM and TEM) images confirmed the preparation of smooth, bead-free, and continuous fibers that formed clear core-shell structures. For further studies, nanofiber mats were cross-linked by heat treatment to avoid rapid disintegration in water and improve both mechanical properties and drug release. The release profile of curcumin and vancomycin indicated an initial burst release, continued by the extended release of both drugs within 72 hours. Rabbit corneal cells demonstrated high rates of proliferation when evaluated using a cell metabolism assay. Finally, the therapeutic efficiency of core/shell nanofibers in healing cornea alkali burn was studied by microscopic and macroscopic observation, fluorescence staining, and hematoxylin-eosin assay on rabbit eyes. The anti-inflammatory activity of fabricated fibers was evaluated by enzyme-linked immunosorbent assay and Immunofluorescence analysis. In conclusion, using a robust array of in vitro and in vivo experiments this study demonstrated the ability of the dual-drug carriers to promote corneal re-epithelialization, minimize inflammation, and inhibit corneal neovascularization. Since these parameters are critical to the healing of corneal wounds from alkali burns, we suggest that this discovery represents a promising future therapeutic agent that warrants further study in humans.
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Affiliation(s)
- Malihe Sadat Razavi
- Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Pedram Ebrahimnejad
- Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran; Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Hamid Akbari Javar
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Thomas A Weppelmann
- Department of Ophthalmology, Morsani College of Medicine, University of South Florida, Tampa, FL, United States of America
| | - Jafar Akbari
- Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Fahimeh Asadi Amoli
- Ophthalmic Pathology Department, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Atyabi
- Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Rassoul Dinarvand
- Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Leicester School of Pharmacy, Leicester Institute for Pharmaceutical Innovation, De Montfort University, Leicester, UK.
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Carletti P, Sepulveda Beltran PA, Levine H, Dubovy SR, Perez VL, Amescua G. Long-Term Comprehensive Management of Bilateral Limbal Stem Cell Deficiency Secondary to Severe Chemical Burn: 10 Years of Follow-Up. Ocul Immunol Inflamm 2023; 31:1629-1634. [PMID: 35816015 DOI: 10.1080/09273948.2022.2090965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 06/13/2022] [Indexed: 10/17/2022]
Abstract
PURPOSE To describe the long-term management of bilateral limbal stem cell deficiency secondary to a severe chemical burn. METHODS Descriptive case report. IMPORTANCE This case highlights the importance of early intervention in ocular chemical burns for the preservation of tissue integrity and avoidance of perforation. We also review the use of proper ocular surface reconstructive techniques to restore the function of the limbal area, as well as the immunomodulatory strategies and follow-up needed for these interventions.
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Affiliation(s)
- Piero Carletti
- Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
| | | | - Harry Levine
- Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Sander R Dubovy
- Florida Lions Ocular Pathology Laboratory, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Victor L Perez
- Duke Eye Center, Duke University, Durham, North Carolina, USA
- Foster Center for Ocular Immunology, Duke University, Durham, North Carolina, USA
| | - Guillermo Amescua
- Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
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Troha K, Vozel D, Arko M, Bedina Zavec A, Dolinar D, Hočevar M, Jan Z, Kisovec M, Kocjančič B, Pađen L, Pajnič M, Penič S, Romolo A, Repar N, Spasovski V, Steiner N, Šuštar V, Iglič A, Drobne D, Kogej K, Battelino S, Kralj-Iglič V. Autologous Platelet and Extracellular Vesicle-Rich Plasma as Therapeutic Fluid: A Review. Int J Mol Sci 2023; 24:3420. [PMID: 36834843 PMCID: PMC9959846 DOI: 10.3390/ijms24043420] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/24/2023] [Accepted: 01/30/2023] [Indexed: 02/11/2023] Open
Abstract
The preparation of autologous platelet and extracellular vesicle-rich plasma (PVRP) has been explored in many medical fields with the aim to benefit from its healing potential. In parallel, efforts are being invested to understand the function and dynamics of PVRP that is complex in its composition and interactions. Some clinical evidence reveals beneficial effects of PVRP, while some report that there were no effects. To optimize the preparation methods, functions and mechanisms of PVRP, its constituents should be better understood. With the intention to promote further studies of autologous therapeutic PVRP, we performed a review on some topics regarding PVRP composition, harvesting, assessment and preservation, and also on clinical experience following PVRP application in humans and animals. Besides the acknowledged actions of platelets, leukocytes and different molecules, we focus on extracellular vesicles that were found abundant in PVRP.
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Affiliation(s)
- Kaja Troha
- Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia
| | - Domen Vozel
- Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia
- University of Ljubljana, Faculty of Medicine, SI-1000 Ljubljana, Slovenia
| | - Matevž Arko
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
| | - Apolonija Bedina Zavec
- Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, SI-1000 Ljubjana, Slovenia
| | - Drago Dolinar
- Department of Orthopedic Surgery, University Medical Centre, Zaloška 9, SI-1000 Ljubljana, Slovenia
- MD-RI Institute for Materials Research in Medicine, Bohoričeva 5, SI-1000 Ljubljana, Slovenia
| | - Matej Hočevar
- Department of Physics and Chemistry of Materials, Institute of Metals and Technology, SI-1000 Ljubljana, Slovenia
| | - Zala Jan
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
| | - Matic Kisovec
- Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, SI-1000 Ljubjana, Slovenia
| | - Boštjan Kocjančič
- Department of Orthopedic Surgery, University Medical Centre, Zaloška 9, SI-1000 Ljubljana, Slovenia
| | - Ljubiša Pađen
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
| | - Manca Pajnič
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
| | - Samo Penič
- University of Ljubljana, Laboratory of Physics, Faculty of Electrical Engineering, SI-1000 Ljubljana, Slovenia
| | - Anna Romolo
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
- University of Ljubljana, Laboratory of Physics, Faculty of Electrical Engineering, SI-1000 Ljubljana, Slovenia
| | - Neža Repar
- University of Ljubljana, Research Group for Nanobiology and Nanotoxicology, Biotechnical Faculty, SI-1000 Ljubljana, Slovenia
| | - Vesna Spasovski
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
- Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia
| | - Nejc Steiner
- Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia
| | - Vid Šuštar
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
| | - Aleš Iglič
- University of Ljubljana, Laboratory of Physics, Faculty of Electrical Engineering, SI-1000 Ljubljana, Slovenia
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Medicine, SI-1000 Ljubljana, Slovenia
| | - Damjana Drobne
- University of Ljubljana, Research Group for Nanobiology and Nanotoxicology, Biotechnical Faculty, SI-1000 Ljubljana, Slovenia
| | - Ksenija Kogej
- University of Ljubljana, Chair of Physical Chemistry, Faculty of Chemistry and Chemical Technology, SI-1000 Ljubljana, Slovenia
| | - Saba Battelino
- Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia
- University of Ljubljana, Faculty of Medicine, SI-1000 Ljubljana, Slovenia
| | - Veronika Kralj-Iglič
- University of Ljubljana, Laboratory of Clinical Biophysics, Faculty of Health Sciences, SI-1000 Ljubljana, Slovenia
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Mini-Conjunctival Limbal Autograft (Mini-CLAU) Using Platelet-Rich Plasma Eye Drops (E-PRP): A Case Series. Cornea 2022:00003226-990000000-00145. [PMID: 36730781 DOI: 10.1097/ico.0000000000003156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 08/14/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE The purpose of this study was to introduce a new method of limbal stem cell transplantation using autologous platelet-rich plasma (E-PRP) eye drops for unilateral total limbal stem cell deficiency. METHODS Patients with total unilateral limbal stem cell deficiency due to chemical burn underwent mini-conjunctival limbal autograft using autologous E-PRP drops. One small limbal block, measuring 2 × 2 mm, was harvested from the patients' contralateral healthy eye and transplanted to the diseased eye. All patients received E-PRP drops until achieving complete corneal epithelialization. Subsequent corneal transplantation was performed in eyes with significant stromal opacification. Corneal buttons obtained during corneal transplantation underwent immunohistochemistry for the evaluation of limbal stem cell markers (ABCG2 and P63). Visual acuity, epithelial healing, corneal clarity, and regression of corneal conjunctivalization/vascularization were evaluated after surgery. RESULTS Ten patients with acid (n = 7) or alkali (n = 3) burn were included. The mean follow-up period was 21.7 ± 5.8 months (range, 12-32 months). Corneas were completely reepithelialized within 14.9 ± 3.5 days (range, 11-21 days). Corneal conjunctivalization/vascularization dramatically regressed 1 to 2 months after surgery in all cases, and corneal clarity considerably improved in 7 patients. In the 3 eyes with significant stromal opacification, subsequent optical penetrating keratoplasty was performed. The ocular surface was stable throughout the follow-up period in all eyes. BSCVA improved to 0.60 ± 0.0.32 and 0.46 ± 0.0.25 logMAR in eyes with and without corneal transplantation, respectively, at the final follow-up visit. ABCG2 and P63 markers were detected on corneal buttons after keratoplasty. CONCLUSIONS Based on our clinical and laboratory findings, mini-conjunctival limbal autograft using E-PRP can be considered as a promising alternative to ocular surface reconstruction.
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Singh VK, Sharma P, Vaksh UKS, Chandra R. Current approaches for the regeneration and reconstruction of ocular surface in dry eye. Front Med (Lausanne) 2022; 9:885780. [PMID: 36213677 PMCID: PMC9544815 DOI: 10.3389/fmed.2022.885780] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 08/18/2022] [Indexed: 11/13/2022] Open
Abstract
Significant research revealed the preocular tear film composition and regulations that remain vital for maintaining Ocular surface functional integrity. Inflammation triggered by many factors is the hallmark of Ocular surface disorders or dry eyes syndrome (DES). The tear deficiencies may lead to ocular surface desiccation, corneal ulceration and/or perforation, higher rates of infectious disease, and the risk of severe visual impairment and blindness. Clinical management remains largely supportive, palliative, and frequent, lifelong use of different lubricating agents. However, few advancements such as punctal plugs, non-steroidal anti-inflammatory drugs, and salivary gland autografts are of limited use. Cell-based therapies, tissue engineering, and regenerative medicine, have recently evolved as long-term cures for many diseases, including ophthalmic diseases. The present article focuses on the different regenerative medicine and reconstruction/bioengineered lacrimal gland formation strategies reported so far, along with their limiting factors and feasibility as an effective cure in future.
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Affiliation(s)
- Vimal Kishor Singh
- Department of Biomedical Engineering, Amity School of Engineering and Technology, Amity University, Noida, Uttar Pradesh, India
- *Correspondence: Vimal Kishor Singh ; ;
| | - Pallavi Sharma
- Tissue Engineering and Regenerative Medicine Research Lab, Department of Biomedical Engineering, Amity School of Engineering and Technology, Amity University, Noida, Uttar Pradesh, India
| | - Uttkarsh Kumar Sharma Vaksh
- Tissue Engineering and Regenerative Medicine Research Lab, Department of Biomedical Engineering, Amity School of Engineering and Technology, Amity University, Gurgaon, Haryana, India
| | - Ramesh Chandra
- Institute of Nanomedical Sciences, University of Delhi, Delhi, India
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15
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Sugar A, Hussain M, Chamberlain W, Dana R, Kelly DP, Ta C, Irvine J, Daluvoy M, Perez V, Olson J, Jhanji V, Walts TA, Stulting RD, Waller EK, Jagirdar N. A Randomized Trial of Topical Fibrinogen-Depleted Human Platelet Lysate Treatment of Dry Eye Secondary to Chronic Graft-versus-Host Disease. OPHTHALMOLOGY SCIENCE 2022; 2:100176. [PMID: 36245754 PMCID: PMC9562362 DOI: 10.1016/j.xops.2022.100176] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 05/25/2022] [Accepted: 05/26/2022] [Indexed: 11/29/2022]
Abstract
Purpose The purpose of the study was to evaluate, as a pilot trial, safety and tolerability of CAM-101 10% and 30% topical ophthalmic fibrinogen-depleted human platelet lysate (FD hPL) solution in patients with dry eye disease (DED) secondary to graft-versus-host disease (GvHD) after 6 weeks of treatment. Design A phase I/II, pilot, prospective, multicenter, randomized, double-masked clinical trial. Participants Patients with DED secondary to GvHD. Methods Sixty-four adult patients were stratified by "symptom severity" (Ocular Surface Disease Index [OSDI], ocular discomfort Visual Analog Scale (VAS), ocular symptom frequency, and use of artificial tears) and then randomized 1:1:1 to CAM-101 (FD hPL) at 10% or 30% concentration or an electrolyte (Plasma-Lyte A) vehicle control, 1 drop in both eyes, 4 times daily, for 42 days. After 42 days, control patients were offered 42 days of open-label treatment with 30% FD hPL. Main Outcome Measures Primary outcome safety measures were ocular and systemic adverse events and the number of patients in each group with clinically significant change from normal to abnormal in any ocular findings. Secondary outcomes were changes from baseline to day 42 in ocular discomfort, OSDI, fluorescein corneal staining, and lissamine green conjunctival staining relative to the vehicle control. The ocular symptom frequency was assessed on a 100-point VAS. Results FD hPL 10% and 30% were safe and well tolerated. Relative to the vehicle control, significant decreases from baseline to day 42 were seen in the FD hPL 30% group with regard to ocular discomfort (mean decrease = -18.04; P = 0.018), frequency of burning/stinging (-20.23; P = 0.022), eye discomfort (-32.97; P < 0.001), eye dryness (-21.61; P = 0.020), pain (-15.12; P = 0.044), photophobia (-24.33; P = 0.0125), and grittiness (-20.08; P = 0.0185). Decreases were also seen for itching and foreign body sensation, though not statistically significant. Improvements were seen in tear breakup time (mean increase = 1.30 seconds; P = 0.082) and the investigator's global evaluation 4-point scale (mean decrease = -0.86; P = 0.026). Corneal fluorescein staining was not improved. The OSDI had a mean decrease of -8.88 compared to the vehicle, although not statistically significant. Conclusions Fibrinogen-depleted human platelet lysate appears to be well tolerated, with no significant toxicity at concentrations of 10% and 30%. These initial data suggest some efficacy, especially for subjective outcome measures relative to baseline assessments and treatment with the vehicle, but larger studies are needed to confirm these effects.
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Key Words
- AE, adverse event
- ASTs, autologous serum tears
- CI, confidence interval
- DED, dry eye disease
- Dry eye disease
- FD hPL, fibrinogen-depleted human platelet lysate
- Graft versus host disease
- GvHD, graft-versus-host disease
- HSCT, hematopoietic stem cell transplant
- Human platelet
- OSDI, ocular surface disease index
- Ocular surface
- PRP, platelet-rich plasma
- SAE, severe adverse event
- Serum tears
- VAS, Visual Analog Scale
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Affiliation(s)
- Alan Sugar
- WK Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan
| | - Munira Hussain
- WK Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan
| | - Winston Chamberlain
- Casey Eye Institute, and Department of Ophthalmology, Oregon Health and Science University, Portland, Oregon
| | - Reza Dana
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
| | | | - Christopher Ta
- Department of Ophthalmology, School of Medicine, Stanford University, Stanford, California
| | - John Irvine
- Doheny Eye Center, UCLA, Los Angeles, California
| | | | - Victor Perez
- Duke University Eye Center, Durham, North Carolina
| | - Joshua Olson
- Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota
| | - Vishal Jhanji
- UPMC Eye Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | | | - Robert Doyle Stulting
- Cambium Medical Technologies LLC, Atlanta, Georgia
- Woolfson Eye Institute, Atlanta, Georgia
| | - Edmund K. Waller
- Cambium Medical Technologies LLC, Atlanta, Georgia
- Winship Cancer Institute of Emory University, Atlanta, Georgia
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Murtaza F, Toameh D, Chiu HH, Tam ES, Somani S. Autologous Platelet‐Rich Plasma Drops for Evaporative Dry Eye Disease from Meibomian Gland Dysfunction: A Pilot Study. Clin Ophthalmol 2022; 16:2199-2208. [PMID: 35821787 PMCID: PMC9271282 DOI: 10.2147/opth.s367807] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 06/22/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose To evaluate the effects of autologous platelet‐rich plasma (PRP) drops for evaporative dry eye (EDE) disease from meibomian gland dysfunction (MGD). Methods This is a retrospective, consecutive case series of 20 eyes of 10 patients with EDE from MGD treated with PRP drops from November 2020 to November 2021 at a single outpatient clinic in Ontario, Canada. PRP drops were prepared from whole blood using a two-step centrifugation method. Patients were instructed to instill these drops six times daily for 4 weeks. The Canadian Dry Eye Assessment (CDEA) questionnaire score, patient subjective assessment (PSA) score, first and average non-invasive break-up times (f/a NIBUT), tear meniscus height (TMH), bulbar redness (BR), and meibograph grade (MG) were measured before and after the treatment course. Results Significant improvements in dry eye symptoms and tear film parameters were observed. Dry eye symptoms significantly improved as per the CDEA (mean difference (MD) = −5.45, 95% confidence interval (CI) = [−7.9, −3.1], p<0.001) and PSA (MD = −2.6, 95% CI = [−3.9, −1.2], p<0.001). There were significant improvements in tear film parameters including fNIBUT (MD = 3.85s, 95% CI = [1.2, 6.8], p=0.006), aNIBUT (MD = −6.81s, 95% CI = [5.7, 11.1], p<0.001) and TMH (MD = 0.08, 95% CI = [0.003, 0.2], p=0.045). There was an improvement in conjunctival injection as measured by BR (MD = −0.36, 95% CI = [−0.4, −0.15], p=0.373). Five eyes experienced a one-grade improvement in MG (p=0.453), and none experienced worsening in MG with treatment. No temporary or permanent adverse effects were noted. Conclusion Four weeks of PRP therapy resulted in significant functional improvements in dry eye symptoms and tear film quality and quantity. Improvements in conjunctival injection and microstructural improvements in meibomian glands were also observed in some eyes. Overall, PRP is a promising treatment option for patients with EDE from MGD refractory to conventional treatments.
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Affiliation(s)
- Fahmeeda Murtaza
- Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Dana Toameh
- Uptown Eye Specialists, Vaughan, Ontario, Canada
| | - Hannah H Chiu
- Uptown Eye Specialists, Vaughan, Ontario, Canada
- Division of Ophthalmology, William Osler Health System, Brampton, Ontario, Canada
- Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, Ontario, Canada
| | - Eric S Tam
- Uptown Eye Specialists, Vaughan, Ontario, Canada
- Division of Ophthalmology, William Osler Health System, Brampton, Ontario, Canada
- Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, Ontario, Canada
| | - Sohel Somani
- Uptown Eye Specialists, Vaughan, Ontario, Canada
- Division of Ophthalmology, William Osler Health System, Brampton, Ontario, Canada
- Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, Ontario, Canada
- Correspondence: Sohel Somani, 401-7900 Hurontario Street, Brampton, Ontario, L6Y 0P6, Canada, Tel +416 292-0330, Fax +416 292-0331, Email
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Mallone F, Marenco M, Giustolisi R, Plateroti R, Lambiase A. Platelet-Rich Plasma (PRP) to promote corneal healing in firework-related ocular burn and total limbal stem cell deficiency (LSCD). Eur J Ophthalmol 2022; 33:NP18-NP22. [PMID: 35139684 DOI: 10.1177/11206721221080004] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
PURPOSE To report the case of persistent corneal epithelial defect in total limbal stem cell deficiency (LSCD) after severe firework-related ocular burn treated with autologous Platelet-Rich Plasma (PRP). CASE DESCRIPTION A young patient, victim of fireworks trauma, presented with a large persistent epithelial defect affecting the central cornea of his left eye and progressing to stromal melting, in the context of grade VI ocular surface burn with 12 h limbal involvement. Impression cytology to the cornea confirmed a complete LSCD. Assessment of corneal sensitivity by Cochet Bonnet esthesiometer revealed complete corneal anesthesia. Based on progressive clinical worsening under conventional therapy, the patient was started on very pure autologous PRP eye drops obtained using the Hy-Tissue PRP® technology. Six times a day eye drops administration for 30 days was scheduled in the affected eye. At the end of treatment, the epithelial defect had disappeared being replaced by advancing conjunctiva. CONCLUSION Our findings provide information on management of ocular burns from fireworks, a subject of current interest and concern. Autologous PRP eye drops prepared using the Hy-Tissue PRP® system and administered in the presence of total LSCD and complete corneal anesthesia, prevented corneal stromal melting to progress and allowed the ocular surface epithelial coverage to re-establish. This paved the way for later successful restorative and reconstructive intervention. Also, first description of the Hy-tissue PRP procedure for ophthalmological use is reported.
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Affiliation(s)
- Fabiana Mallone
- Department of Sense Organs, 9311Sapienza University of Rome, Rome, Italy
| | - Marco Marenco
- Department of Sense Organs, 9311Sapienza University of Rome, Rome, Italy
| | - Rosalia Giustolisi
- Department of Sense Organs, 9311Sapienza University of Rome, Rome, Italy
| | - Rocco Plateroti
- Department of Sense Organs, 9311Sapienza University of Rome, Rome, Italy
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Effect of Platelet-Rich Plasma on Corneal Epithelial Healing after Phototherapeutic Keratectomy: An Intraindividual Contralateral Randomized Study. BIOMED RESEARCH INTERNATIONAL 2021; 2021:5752248. [PMID: 34873572 PMCID: PMC8643227 DOI: 10.1155/2021/5752248] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 09/09/2021] [Accepted: 11/16/2021] [Indexed: 12/04/2022]
Abstract
Purpose To assess the effect of platelet-rich plasma (PRP) on the healing response of the corneal epithelium in eyes undergoing phototherapeutic keratectomy (PTK). Methods We prospectively examined 20 eyes of 10 patients undergoing bilateral PTK for granular corneal dystrophy or band keratopathy. Patients were randomly assigned to start topical administration of PRP ophthalmic suspension (PRP group) or artificial tears (control group) 4 times daily for 2 weeks. Immediately, 1, and 2 days, and 1 week after PTK, we quantitatively measured the staining area of the corneal epithelium, using slit-lamp photography. We also determined the subjective symptoms and the satisfaction, using the visual analogue system (VAS). Results The staining area in the PRP group was significantly smaller than that in the control group on days 1 and 2 (Wilcoxon signed-rank test, p = 0.022 and p = 0.017, respectively), but not on day 7 (p = 0.317). The recovery rate of the corneal epithelium in the PRP group was significantly higher than that in the control group on days 1 and 2 (p = 0.022 and p = 0.017, respectively), but not on day 7 (p = 0.317). We found no significant differences in pain (p = 0.139), foreign body sensation (p = 0.108), epiphora (p = 1.000), or satisfaction (p = 0.295), between the two groups. Postoperative complications did not occur in any of the eyes in the study. Conclusions The PRP treatment was effective for enhancing corneal epithelial recovery in the early postoperative period, without significant adverse events, in post-PTK-treated eyes, suggesting that it may hold promise as one of the treatment options for treating such postsurgical patients.
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Peláez P, Damiá E, Torres-Torrillas M, Chicharro D, Cuervo B, Miguel L, del Romero A, Carrillo JM, Sopena JJ, Rubio M. Cell and Cell Free Therapies in Osteoarthritis. Biomedicines 2021; 9:1726. [PMID: 34829953 PMCID: PMC8615373 DOI: 10.3390/biomedicines9111726] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/12/2021] [Accepted: 11/16/2021] [Indexed: 12/18/2022] Open
Abstract
Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact on patients' function, decreasing quality of life. There are many limitations regarding OA conventional therapies-pharmacological therapy can cause gastrointestinal, renal, and cardiac adverse effects, and some of them could even be a threat to life. On the other hand, surgical options, such as microfracture, have been used for the last 20 years, but hyaline cartilage has a limited regeneration capacity. In recent years, the interest in new therapies, such as cell-based and cell-free therapies, has been considerably increasing. The purpose of this review is to describe and compare bioregenerative therapies' efficacy for OA, with particular emphasis on the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). In OA, these therapies might be an alternative and less invasive treatment than surgery, and a more effective option than conventional therapies.
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Affiliation(s)
- Pau Peláez
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Elena Damiá
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Marta Torres-Torrillas
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Deborah Chicharro
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Belén Cuervo
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Laura Miguel
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Ayla del Romero
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Jose Maria Carrillo
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Joaquín J. Sopena
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
| | - Mónica Rubio
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain; (P.P.); (M.T.-T.); (D.C.); (B.C.); (L.M.); (A.d.R.); (J.M.C.); (J.J.S.); (M.R.)
- Garcia Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, 08006 Barcelona, Spain
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20
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Promoting limbal stem cells proliferation and maintenance using post-thaw human amniotic membranes fortified by platelet lysate. GENE REPORTS 2021. [DOI: 10.1016/j.genrep.2021.101084] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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21
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Gandolfi M, Brandão C, Pellizon C, Hirota I, Barros R, Hussein A, Merlini N, Takahira R, Mesquita L. Allogenic platelet-rich plasma in induced ulcers in rat’s cornea. ARQ BRAS MED VET ZOO 2021. [DOI: 10.1590/1678-4162-12214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
ABSTRACT The objective in this study was to evaluate the clinic effect of applying allogenic platelet-rich plasma (PRP) heated or not, for treating cornea ulcers, including the dosage of PDGF-BB in the cornea. The ulcers were induced, standardizing the left eye from 81 rats (Ratus norvegicus, albinus variety), assigned randomly into three groups (N=27): control group (CG) which did not receive any topic treatment; heated PRP group (GA) and PRP group (GP), which received topical treatment every eight hours for five days. Each group underwent evaluation at 24 hours (M1), three days (M3) and five days (M5). The clinical exam evaluated the opacity, vascularization and corneal repair. The corneal PDGF-BB was dosed through the ELISA method. The corneal opacity was decreased in PRP-treated animals (GA and GP) and corneal repair time reduced when compared to CG at M1 and M5. Furthermore, GP showed greater vascularization at M3 compared to M1. Applied allogenic PRP eye drops, heated or not, speed up corneal healing, and reduce corneal repair time. However, the corneal PDGF concentration was not altered in any of the treatments.
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Affiliation(s)
| | | | | | | | - R. Barros
- Universidade Estadual Paulista, Brazil
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22
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Tsui MC, Liu JY, Chu HS, Chen WL. Toxic keratopathy related to antiseptics in nonocular surgery. Taiwan J Ophthalmol 2021; 11:179-182. [PMID: 34295625 PMCID: PMC8259519 DOI: 10.4103/tjo.tjo_5_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 02/07/2021] [Indexed: 11/17/2022] Open
Abstract
Antiseptics, especially those containing ethanol, are toxic to the ocular surface. Here, we report a 5-year-old girl with antiseptic-related eye injury following an uneventful bilateral tonsillectomy under general anesthesia. Before surgery, her eyes were protected and disinfection of perioral skin with ethanol-containing chlorhexidine followed. Whitening of the lower half of her right ocular surface was found after the surgery, and this indicated severe chemical burn. Prompt irrigation with normal saline, instillation of topical medication, and application of amniotic membrane containing device were performed, which led to a satisfactory result. Toxic eye injury could happen in head and neck surgeries under general anesthesia. Causes of ocular injury include improper eye protection, head positions leading to accumulation of excessive antiseptics, and improper usage of ethanol-containing antiseptics for skin preparation. The use of ethanol-free antiseptic solutions in the peri-ocular region and proper protection of eyes may reduce the risk of severe ocular surface injury in nonocular surgeries.
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Affiliation(s)
- Mei-Chi Tsui
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
| | - Jen-Yu Liu
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsiao-Sang Chu
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.,Advanced Ocular Surface and Corneal Nerve Regeneration Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Wei-Li Chen
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.,Advanced Ocular Surface and Corneal Nerve Regeneration Center, National Taiwan University Hospital, Taipei, Taiwan.,Department of Ophthalmology, College of Medicine, National Taiwan University, Taipei, Taiwan
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23
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Gao M, Chen Y, Zhai F, Liu Z, Liu Q, Wang Z. The effect of cultured autologous oral mucosal epithelial cells on ocular surface reconstruction. Arch Med Sci 2021; 20:813-821. [PMID: 39050175 PMCID: PMC11264149 DOI: 10.5114/aoms/115576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 12/20/2019] [Indexed: 07/27/2024] Open
Abstract
Introduction Oral epithelial cells were recently shown to be able to differentiate into corneal epithelium, and the efficacy of cultured autologous oral mucosal epithelial cells (CAOMEC) has been suggested by the presence of epithelium replacement. Therefore, the aim of this study was to evaluate the treatment outcome in limbal stem cell deficiency (LSCD) by adding CAOMEC to regular amniotic membrane (AM) treatment. Material and methods Eyes with LSCD were randomized to two groups to undergo either autologous oral mucosal epithelial cell sheet (CAOMECS) combined with AM transplantation (A group) or AM transplantation alone (B group). Clinical outcome measures were corneal epithelium healing, best corrected visual acuity, symblepharon, corneal transparency, corneal neovascularization and ocular surface inflammation. Results The normal corneal epithelialization rate in group A (73.33%) was higher than that in group B (35.48%), and the average healing time was shorter (3.45 ±2.12 weeks vs. 4.64 ±1.63 weeks). The symblepharon in the above two groups was improved in the first 3 months after surgery, but after 6 months, part of the B group had recurrence. In improving corneal transparency, group A has obvious advantages. Corneal neovascularization (CNV) was improved to some extent in the first 3 months after surgery, but group A (1.47 ±0.64) was better than group B (1.94 ±0.85) after 6 months. Both groups can improve the inflammatory state to some extent. Conclusions The transplantation of CAOMECS offers a viable and safe alternative in the reconstruction of a stable ocular surface. The effect is better than that of traditional AM transplantation, mainly in promoting corneal epithelialization, improving ocular surface structure, and reducing fiber and vascular infiltration.
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Affiliation(s)
- Minghong Gao
- The General Hospital of Northern Theater Command, Shenyang, China
| | - Yingxin Chen
- The General Hospital of Northern Theater Command, Shenyang, China
| | - Fengying Zhai
- The General Hospital of Northern Theater Command, Shenyang, China
| | - Zhiling Liu
- The General Hospital of Northern Theater Command, Shenyang, China
| | - Qiming Liu
- The General Hospital of Northern Theater Command, Shenyang, China
| | - Ziyue Wang
- The General Hospital of Northern Theater Command, Shenyang, China
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24
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[Acute chemical burns of the eye : S1 guidelines of the German Ophthalmological Society (DOG) and the Professional Association of German Ophthalmologists (BVA)]. Ophthalmologe 2021; 118:103-116. [PMID: 33666702 DOI: 10.1007/s00347-021-01326-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/19/2021] [Indexed: 11/29/2022]
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25
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Panda BB, Mohapatra S, Parida S. Update on the role of Eye platelet-rich plasma (E-PRP) in the treatment of ocular surface disorders. INDIAN JOURNAL OF CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 2020; 6:487-496. [DOI: 10.18231/j.ijceo.2020.106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2024]
Abstract
Platelet rich plasma is the highly concentrated form of autologous human platelets in a small amount of plasma which contains important growth factors and plasma proteins that plays a significant role in wound healing process by epithelial differentiation and collagen bundle organization. In this article, we aim to provide an update on the current literature regarding the eye platelet rich plasma, its methods of preparation, physiological and biochemical properties, its clinical applications, safety and efficacy as compared to other blood derived products etc. In ophthalmology, this product is being used in the management of symptomatic dry eyes, corneal ulcers, periocular chemical and thermal burns, Idiopathic macular hole, Skin rejuvenation post Blepharoplasties and more recently actinic elastosis in the lower eyelid regions. The role of eye platelet rich plasma in ocular surface disorders has been sparsely studied in literature with more studies and reports on the application of autologous and allogeneic serum eye drops and therefore, it becomes very important to update ourselves with more studies in this topic to prove the efficiency of this blood derived product. Moreover, the role of other platelet derived products like platelet rich growth factors, platelet lysate in ocular surface disorders have also been discussed.
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26
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Kao YC, Lin DZ, Lee SL, Chen C, Wang HJ, Chiu WK. Assisted therapy with platelet-rich plasma for burn patients: A meta-analysis and systematic review. Burns 2020; 47:1012-1023. [PMID: 33962831 DOI: 10.1016/j.burns.2020.11.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 10/08/2020] [Accepted: 11/19/2020] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Platelet-rich plasma (PRP) therapy has been used in different medical fields, but its effectiveness in burn wound healing remains debatable. In this study, we performed a systematic review and meta-analysis of the available evidence on burn patients treated with PRP to evaluate the safety and efficacy of the treatment. METHODS Randomized controlled trials evaluating the efficacy of PRP in patients with burn injuries were selected. Eligible retrospective studies were abstracted and assessed for the risk of bias by two reviewers and results of mean time to complete epithelization and wound closure rate in the included studies were analyzed. Studies on the correlation between PRP and burn wound healing published in English or Chinese before March 2020 were retrieved from PubMed. RESULTS Eight studies (including 449 patients) met our inclusion criteria. Qualitative analysis revealed that compared with the control group, the PRP group had significantly better wound closure rates at weeks 2 (mean difference (MD): 12.79 [95% confidence interval (CI): 7.08, 18.49]; I2: 0%; p < 0.0001) and 3 (MD: 12.66 [95% CI: 5.97, 19.34]; I2: 55%; p = 0.0002) and time to complete epithelialization (MD: -3.45 [95% CI: -4.87, -2.04] (days); I2: 0%; p < 0.00001). There was no significant difference in infection rate or graft take rate. CONCLUSIONS PRP application can accelerate wound closure, however, it has no effect on the rates of wound infection and graft take rate.
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Affiliation(s)
- Yu-Chien Kao
- School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Dai-Zhu Lin
- School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Sheng-Lian Lee
- Division of Plastic Surgery, Department of Surgery, Taipei Municipal Wanfang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Chiehfeng Chen
- Division of Plastic Surgery, Department of Surgery, Taipei Municipal Wanfang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Cochrane Taiwan, Taipei Medical University, Taipei, Taiwan.
| | - Hsian-Jenn Wang
- Division of Plastic Surgery, Department of Surgery, Taipei Municipal Wanfang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Wen-Kuan Chiu
- Division of Plastic Surgery, Department of Surgery, Taipei Municipal Wanfang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan.
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27
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Xu PC, Xuan M, Cheng B. Effects and mechanism of platelet-rich plasma on military drill injury: a review. Mil Med Res 2020; 7:56. [PMID: 33220706 PMCID: PMC7680596 DOI: 10.1186/s40779-020-00285-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 11/04/2020] [Indexed: 02/07/2023] Open
Abstract
Military drill injury is a significant part of military medical research. The increase of training intensity and changes in training methods lead to differences in injury types. The ideal therapeutic modality should allow rapid healing at a reasonable cost and minimize impact on patients' life. Platelet -rich plasma (PRP), a platelet concentrate, is rich in a variety of growth factors and widely used clinically as a minimally invasive treatment. It plays an important role in injury repair and rehabilitation. In this article, we review the therapeutic role of PRP in military drill injury and its possible underlying mechanisms, with a focus on plantar fasciitis, stress fractures and other common injuries, in order to provide basic support for military reserve.
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Affiliation(s)
- Peng-Cheng Xu
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command of Chinese PLA, No. 111 Liuhua Road, Yuexiu District, Guangzhou, 510010, Guangdong Province, China
| | - Min Xuan
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command of Chinese PLA, No. 111 Liuhua Road, Yuexiu District, Guangzhou, 510010, Guangdong Province, China
| | - Biao Cheng
- Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command of Chinese PLA, No. 111 Liuhua Road, Yuexiu District, Guangzhou, 510010, Guangdong Province, China.
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28
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Gouveia RM, Connon CJ. Biomechanical Modulation Therapy-A Stem Cell Therapy Without Stem Cells for the Treatment of Severe Ocular Burns. Transl Vis Sci Technol 2020; 9:5. [PMID: 33240564 PMCID: PMC7671857 DOI: 10.1167/tvst.9.12.5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 09/07/2020] [Indexed: 12/16/2022] Open
Abstract
Ocular injuries caused by chemical and thermal burns are often unmanageable and frequently result in disfigurement, corneal haze/opacification, and vision loss. Currently, a considerable number of surgical and pharmacological approaches are available to treat such injuries at either an acute or a chronic stage. However, these existing interventions are mainly directed at (and limited to) suppressing corneal inflammation and neovascularization while promoting re-epithelialization. Reconstruction of the ocular surface represents a suitable but last-option recourse in cases where epithelial healing is severely impaired, such as due to limbal stem cell deficiency. In this concise review, we discuss how biomechanical modulation therapy (BMT) may represent a more effective approach to promoting the regeneration of ocular tissues affected by burn injuries via restoration of the limbal stem cell niche. Specifically, the scientific basis supporting this new therapeutic modality is described, along with our growing understanding of the role that tissue biomechanics plays in stem cell fate and function. The potential impact of BMT as a future treatment option for the management of injuries affecting tissue compliance is also further discussed.
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Affiliation(s)
- Ricardo M Gouveia
- Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne, UK
| | - Che J Connon
- Biosciences Institute, Faculty of Medical Sciences, The Medical School, Newcastle University, Newcastle upon Tyne, UK
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29
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Dua HS, Ting DSJ, Al Saadi A, Said DG. Chemical eye injury: pathophysiology, assessment and management. Eye (Lond) 2020; 34:2001-2019. [PMID: 32572184 PMCID: PMC7784957 DOI: 10.1038/s41433-020-1026-6] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 05/27/2020] [Accepted: 06/04/2020] [Indexed: 11/09/2022] Open
Abstract
Chemical eye injury (CEI) is an acute emergency which can threaten sight and life. These commonly occur at home or the workplace with the former being generally mild and the latter more severe and bilateral. Major workplace accidents involve other parts of the body and can be associated with inhalation or ingestion of the chemical. Alkali injuries cause damage by saponification of tissue and deeper penetration as a consequence. Acid injuries cause rapid coagulation of tissue, which impedes penetration and limits damage. Irritants such as alcohols, cause superficial epithelial denudation. Severe chemical insult can affect all anterior segment structures causing iris, pupil and lens abnormalities. Eye pressure is variably affected and can be low or high or start as one and rapidly change to the other. Chorioretinal changes in the form of vasculopathy are seen and ascribed to be secondary to anterior segment inflammation rather than due to the direct effect of CEI. Final outcome related to structure and function is determined by the injurious agent, duration of exposure, nature of treatment and the rapidity with which it is instituted. Prevention of further damage by profuse and prolonged eye wash, after ascertaining pH of both eyes, together with exploration and removal of all particulate matter, is the key. Other management principles include a complete and thorough assessment, control of inflammation, facilitation of healing and prevention and management of sequelae and complications. Intraocular pressure is often forgotten and must be assessed and managed. Management often requires a multidisciplinary approach.
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Affiliation(s)
- Harminder S Dua
- Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK.
- Department of Ophthalmology, Queen's Medical Centre, Nottingham, UK.
| | - Darren Shu Jeng Ting
- Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK
- Department of Ophthalmology, Queen's Medical Centre, Nottingham, UK
| | - Ahmed Al Saadi
- Department of Ophthalmology, Zayed Military Hospital, Abu Dhabi, UAE
| | - Dalia G Said
- Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK
- Department of Ophthalmology, Queen's Medical Centre, Nottingham, UK
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30
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You J, Hodge C, Hoque M, Petsoglou C, Sutton G. Human Platelets and Derived Products in Treating Ocular Surface Diseases - A Systematic Review. Clin Ophthalmol 2020; 14:3195-3210. [PMID: 33116370 PMCID: PMC7567560 DOI: 10.2147/opth.s265701] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 08/26/2020] [Indexed: 12/26/2022] Open
Abstract
Human platelet products have emerged as an alternative treatment for a range of ocular surface diseases such as dry eye and corneal ulceration. With significant therapeutic potential and increasing popularity, this study aimed to conduct a systematic review to detail the various production methods involved in generating platelet-derived products, compare and analyze clinical findings across available studies, and disseminate the relative advantages, limitations, and challenges of using platelet products to treat ocular surface disease. Thirty-eight clinical studies were identified, excluding studies conducted in animals and non-English language. Studies reported clinical outcomes, which included ocular surface disease index, best-corrected visual acuity, and corneal fluorescein staining. Most clinical studies reported improved patient signs and symptoms with an increasing variety of human platelet products including platelet rich plasma eye drops, human platelet lysate and platelet gels. However, due to variations in production methods, and study designs as well as confusing terminology, it was suggested that characterization of platelet products is needed for proper evaluation across studies.
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Affiliation(s)
- Jingjing You
- Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,School of Optometry and Vision Science, UNSW Sydney, Sydney, NSW, Australia
| | - Chris Hodge
- Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,Vision Eye Institute, Chatswood, Sydney, NSW, Australia.,NSW Tissue Bank, Sydney, NSW, Australia.,Graduate School of Health, University of Technology Sydney, Sydney, NSW, Australia
| | | | - Constantinos Petsoglou
- Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,NSW Tissue Bank, Sydney, NSW, Australia
| | - Gerard Sutton
- Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.,Vision Eye Institute, Chatswood, Sydney, NSW, Australia.,NSW Tissue Bank, Sydney, NSW, Australia
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31
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Soleimani M, Naderan M. Management Strategies of Ocular Chemical Burns: Current Perspectives. Clin Ophthalmol 2020; 14:2687-2699. [PMID: 32982161 PMCID: PMC7501954 DOI: 10.2147/opth.s235873] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 08/20/2020] [Indexed: 11/25/2022] Open
Abstract
Ocular chemical burns are absolute ophthalmic emergencies and require immediate management to minimize devastating sequelae. Management of alkali and acid burns is started at the scene of the accident by copious irrigation. Treatment is directed at improving epithelial integrity and stromal stability, reduction of undue inflammation, and prevention or timely management of complications. To ascertain the best possible outcome, numerous biological medications and surgical interventions have been merged into conventional therapeutic regimens. These include autologous and umbilical cord serum preparations, platelet-rich plasma, amniotic membrane transplantation, limbal stem-cell transplantation, and anti-angiogenic agents.
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Affiliation(s)
- Mohammad Soleimani
- Ocular Trauma and Emergency Department, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Morteza Naderan
- Ocular Trauma and Emergency Department, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
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32
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Serum eye drops for the treatment of ocular surface diseases: a systematic review and meta-analysis. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2019; 17:200-209. [PMID: 31246562 DOI: 10.2450/2019.0080-19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 05/15/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND The use of blood-derived eye drops for topical treatment of ocular surface diseases has progressively increased in recent years. MATERIALS AND METHODS To evaluate the use of serum eye drops in ocular surface disorders, we performed a systematic search of the literature. RESULTS In this systematic review, we included 19 randomised controlled trials (RCTs) investigating the use of serum eye drops in 729 patients compared to controls. For the quantitative synthesis, we included only 10 RCTs conducted in patients with dry eye syndrome comparing autologous serum to artificial tears. At 2-6 weeks, no clear between-group differences in Schirmer test (MD 1.05; 95% CI: -0.17-2.26) and in fluorescein staining (MD -0.61; 95% CI: -1.50-0.28) were found (very low-quality evidence, down-graded for inconsistency, serious risk of biases, and serious imprecision). Slightly higher increase in tear film break-up time (TBUT) scores in autologous serum compared to control (MD 2.68; 95% CI: 1.33-4.03), and greater decrease in ocular surface disease index (OSDI) in autologous serum compared to control (MD -11.17; 95% CI: -16.58 - -5.77) were found (low quality evidence, down-graded for serious risk of bias, and for inconsistency). For the Schirmer test, fluorescein staining and TBUT, data were also available at additional follow-up timing (2-12 months): no clear between-group differences were found, and the quality of the evidence was graded as low/very-low. CONCLUSIONS In patients with dry eye syndrome, it is unclear whether or not the use of autologous serum compared to artificial tears increases Schirmer test and fluorescein staining scores at short-term and medium-/long-term follow up. Some benefit at short-term follow up for the outcome of TBUT and OSDI was observed, but the quality of the evidence was low.
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33
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Bernabei F, Roda M, Buzzi M, Pellegrini M, Giannaccare G, Versura P. Blood-Based Treatments for Severe Dry Eye Disease: The Need of a Consensus. J Clin Med 2019; 8:E1478. [PMID: 31533289 PMCID: PMC6780616 DOI: 10.3390/jcm8091478] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 09/05/2019] [Accepted: 09/12/2019] [Indexed: 01/08/2023] Open
Abstract
The use of blood-based eye drops as therapy for various diseases of the ocular surface has become increasingly popular in ophthalmic practice during recent years. The rationale for their use is based on the promotion of cellular proliferation and migration thanks to the supply of metabolically active substances, in particular growth factors. Blood-derived eye drops have been used for the treatment of several ocular surface disorders, such as dry eye disease, corneal ulcer, persistent epithelial defect, neurotrophic keratitis, ocular surface burn, recurrent corneal erosion, and limbal stem-cell deficiency. Both autologous (from patients themselves) and heterologous (from adult donors or from cord blood sampled at birth)-derived products exist, and each source has specific pros and cons. Despite an extensive literature, several issues are still under debate and the aim of this manuscript is to review the indications, preparation methods and storage, characterization of content, rationale for clinical outcomes, patient stratification, length of treatment, and rationale for repeated treatments at disease relapse. A rationale based on a "5 Ws and 2 Hs" protocol is proposed as a way of thinking, with the attempt to clarify Who, Why, When, Where, What, and How to use these treatment options.
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Affiliation(s)
- Federico Bernabei
- Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| | - Matilde Roda
- Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| | - Marina Buzzi
- Emilia Romagna Cord Blood Bank-Transfusion Service, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| | - Marco Pellegrini
- Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| | - Giuseppe Giannaccare
- Department of Ophthalmology, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy.
| | - Piera Versura
- Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
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Anitua E, Troya M, Pino A. A novel protein-based autologous topical serum for skin regeneration. J Cosmet Dermatol 2019; 19:705-713. [PMID: 31397540 DOI: 10.1111/jocd.13075] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 03/06/2019] [Accepted: 03/18/2019] [Indexed: 12/30/2022]
Abstract
BACKGROUND As skin ages, a functional decrement occurs. To avoid future vulnerability to dermatologic diseases, an optimal cutaneous regeneration is mandatory. Biological therapies based on blood-derived autologous proteins are gaining attention of scientists and dermatologists. OBJECTIVES A novel 100% autologous topical serum has been developed using plasma rich in growth factors technology. The physicochemical characterization and the biologic potential of the novel formulation have been studied. METHODS Rheological and mechanical properties and the biological capacity of the formulation were characterized. Human dermal fibroblast culture and 3D organotypic skin explants were used as in vitro and ex vivo cutaneous models, respectively. RESULTS The autologous topical serum presented an optimal spreadability index and appropriate shear thinning behavior that allowed an easy handling and rapid integration within the cutaneous tissue. The formulation has a high growth factor load with the ability to progressively penetrate into the dermal/epidermal layers of the skin. It is biocompatible and promotes cell proliferation and chemotactic activity. The autologous topical serum promotes the biosynthetic activity of cells by the stimulation of collagen and hyaluronic acid expression. CONCLUSIONS These findings present an in situ and easy to prepare autologous topical serum based on the patient's own blood with physicochemical and bioactive properties that may be used for skin regeneration purposes.
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Affiliation(s)
- Eduardo Anitua
- Eduardo Anitua Foundation, Vitoria, Spain.,BTI - Biotechnology Institute, Vitoria, Spain
| | - María Troya
- BTI - Biotechnology Institute, Vitoria, Spain
| | - Ander Pino
- BTI - Biotechnology Institute, Vitoria, Spain
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García‐Conca V, Abad‐Collado M, Hueso‐Abancens JR, Mengual‐Verdú E, Piñero DP, Aguirre‐Balsalobre F, Molina JC. Efficacy and safety of treatment of hyposecretory dry eye with platelet-rich plasma. Acta Ophthalmol 2019; 97:e170-e178. [PMID: 30450721 DOI: 10.1111/aos.13907] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Accepted: 08/04/2018] [Indexed: 12/27/2022]
Abstract
OBJECTIVE To evaluate and compare the symptomatology and clinical findings in hyposecretory dry eye of the treatment with platelet-rich plasma (PRP) and artificial tears of sodium hyaluronate (SH). METHODS Blind single-centre prospective comparative randomized study including 83 patients with hyposecretory dry eye and mean age of 64.0 years. Two groups were differentiated depending on the treatment applied: 44 patients treated with PRP (PRP group), and 39 patients treated with artificial tears of SH (SH group). Changes in Schimer test, tear osmolarity, corneal and conjunctival staining, tear film break-up time (TF-BUT), conjunctival hyperaemia, dry eye-related symptoms with the Ocular Surface Disease Index questionnaire, and caliciform cell density were evaluated during 30 days of treatment. RESULTS Significantly larger reduction in symptomatology (p < 0.001), visual improvement (p < 0.001), reduction in hyperaemia (p < 0.001), and corneal and conjunctival staining (p < 0.001), increment of Schirmer test outcome (p ≤ 0.005), and reduction of osmolarity were found in the PRP group in both eyes compared to SH group at 15 and 30 days of treatment. Likewise, a significantly higher increment of caliciform cell density (p < 0.001) was found in the PRP group. Strong and statistically significant correlations were found in the PRP group of the change achieved in visual acuity, hyperaemia, osmolarity, and conjunctival and corneal staining with the baseline values of these variables (p < 0.001). CONCLUSION PRP treatment in hyposecretory dry eye induces a more significant positive effect over symptomatology and different dry eye signs than SH, especially in moderate and severe cases.
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Affiliation(s)
| | | | | | | | - David P Piñero
- Department of Optics, Pharmacology and Anatomy University of Alicante Alicante Spain
| | | | - Julio C Molina
- Department of Ophthalmology San Juan University Hospital Alicante Spain
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Alizadeh S, Balagholi S, Baradaran-Rafii A, Delfaza-Baher S, Safi S, Safi H, Dabbaghi R, Kanavi MR. Autologous Platelet-rich Plasma Eye Drops Accelerate Re-epithelialization of Post-keratoplasty Persistent Corneal Epithelial Defects. J Ophthalmic Vis Res 2019; 14:131-135. [PMID: 31114648 PMCID: PMC6504730 DOI: 10.4103/jovr.jovr_279_17] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Purpose: To investigate whether autologous platelet-rich plasma (PRP) eye drops accelerate re-epithelialization of post-keratoplasty persistent corneal epithelial defects (PEDs). Methods: A total of 34 eyes with PEDs after keratoplasty (24 penetrating keratoplasty and 10 deep anterior lamellar keratoplasty) that were refractory to conventional medical treatments were treated with PRP eye drops every 3 hours. PRP eye drops were prepared with a low- and high-speed centrifugation method and final platelet counts were 700,000-800,000 plt/μl. The mean treatment duration for complete re-epithelialization was compared with the mean treatment duration of conventionally treated corneal defects before the PRP treatment by paired t-test. The mean treatment duration was also statistically analyzed between age groups, gender, indications for keratoplasty, and types of keratoplasty using analysis of variance (ANOVA). Results: Treatment with autologous PRP eye drops led to rapid re-epithelialization in all eyes. The mean treatment duration for complete re-epithelialization was 2.47 ± 1.21 weeks, which was significantly shorter than the mean treatment duration of conventionally treated corneal defects before PRP treatment (6.82 ± 1.24 weeks) (P = 0.0001). There was no significant correlation between re-epithelialization time and patients' age, sex, indications for keratoplasty, and techniques of corneal transplantation. Conclusion: Treatment with autologous PRP eye drops is an effective and reliable approach that accelerates re-epithelialization of post-transplantation PEDs.
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Affiliation(s)
- Shaban Alizadeh
- Department of Hematology, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Sahar Balagholi
- Department of Hematology, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Baradaran-Rafii
- Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Siamak Delfaza-Baher
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sare Safi
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Safi
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Rasul Dabbaghi
- Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mozhgan Rezaei Kanavi
- Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Edelmann ML, Mohammed HO, Wakshlag JJ, Ledbetter EC. Clinical trial of adjunctive autologous platelet-rich plasma treatment following diamond-burr debridement for spontaneous chronic corneal epithelial defects in dogs. J Am Vet Med Assoc 2018; 253:1012-1021. [PMID: 30272521 DOI: 10.2460/javma.253.8.1012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To evaluate the effects of adjunctive treatment with autologous platelet-rich plasma (PRP) on corneal reepithelialization, vascularization, and fibrosis in dogs with spontaneous chronic corneal epithelial defects (SCCEDs). DESIGN Randomized, controlled, double-masked clinical trial. ANIMALS 40 client-owned dogs with uncomplicated SCCEDs. PROCEDURES All dogs were treated with diamond-burr epithelial debridement (DBD) of affected eyes, topical tobramycin solution and atropine sulfate ointment application, and Elizabethan collar placement for 4 weeks. Dogs were randomly assigned to topical ocular administration of autologous PRP (n = 20) or artificial tear solution (control group; 20) 4 times daily for 28 days. Recheck examinations were performed approximately 2 and 4 weeks after treatment began to evaluate SCCEDs for corneal reepithelialization, and semiquantitative corneal vascularization and corneal fibrosis scores were assigned according to affected corneal surface area. Results were compared between groups. RESULTS All dogs completed the study. The SCCEDs had completely reepithelialized in 11 (55%) control dogs and 12 (60%) PRP-treated dogs by the 2-week reevaluation, and in 15 (75%) control dogs and 18 (90%) PRP-treated dogs by the 4-week reevaluation. No significant differences were identified between groups in these proportions nor in mean differences from pretreatment scores for corneal vascularization and fibrosis. CONCLUSIONS AND CLINICAL RELEVANCE In this preliminary study involving dogs with uncomplicated SCCEDs, topical PRP administered as an adjunctive treatment following DBD had no significant effect on healing. A larger study is warranted to support or refute these findings and to determine the effects of adjunctive PRP treatment for dogs with complicated SCCEDs.
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Clinical Efficacy of Platelet-Rich Plasma in the Treatment of Neurotrophic Corneal Ulcer. J Ophthalmol 2018; 2018:3538764. [PMID: 30026985 PMCID: PMC6031214 DOI: 10.1155/2018/3538764] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 12/22/2017] [Accepted: 01/15/2018] [Indexed: 12/18/2022] Open
Abstract
Purpose Platelet-rich plasma (PRP) is an autologous blood product without preservatives and rich in proteins and growth factors which make it possible for cells to differentiate, proliferate, and migrate, thus stimulating healing and regeneration of tissues. The aim of this study was to evaluate the efficiency of autologous platelet-rich plasma in the treatment of neurotrophic keratopathy. Methods The study group consists of 25 patients with nonhealing corneal ulcers due to herpes simplex or herpes zoster infection and facial nerve or trigeminal nerve paralysis as a result of a neurosurgical operation caused by a tumour or stroke. The patients were given autologous platelet-rich plasma drops five times a day and additionally preservative-free artificial tears and a vitamin A ointment at night for maximum 3 months. The following were evaluated: best corrected visual acuity (BCVA), healing of corneal surface, subjective symptoms, and changes in corneal thickness with the use of anterior segment optical coherent tomography (AS-OCT). Results BCVA before the treatment was 0.10 ± 0.14, and after the treatment it was –0.3 ± 0.27 (p=0.001). Improved visual acuity and less subjective symptoms were observed in all patients. Complete healing of the ulceration was observed in 20 patients (80%). Four patients (16%) experienced considerable improvement of their clinical condition (reduced size and depth of the ulceration and inflammatory state: smaller conjunctival injection and swelling, improved visual acuity, and less subjective symptoms). In one of the patients, an amniotic membrane was transplanted due to the lack of improvement of his local condition. In all patients, the progression of corneal thinning was stopped. An average corneal thickness in its thinnest point was 322.3 ± 125.8 µm before the treatment, and 404.5 ± 118.7 µm (p < 0.05) after the treatment. None of the patients reported general or local side effects of the treatment. Conclusions Autologous platelet-rich plasma is a blood-based product which seems efficient in the treatment of neurotrophic keratopathy.
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Han SB, Liu YC, Mohamed-Noriega K, Mehta JS. Application of Novel Drugs for Corneal Cell Regeneration. J Ophthalmol 2018; 2018:1215868. [PMID: 29854423 PMCID: PMC5954904 DOI: 10.1155/2018/1215868] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 02/26/2018] [Accepted: 03/27/2018] [Indexed: 11/18/2022] Open
Abstract
Corneal transplantation has been the only treatment method for corneal blindness, which is the major cause of reversible blindness. However, despite the advancement of surgical techniques for corneal transplantation, demand for the surgery can never be met due to a global shortage of donor cornea. The development of bioengineering and pharmaceutical technology provided us with novel drugs and biomaterials that can be used for innovative treatment methods for corneal diseases. In this review, the authors will discuss the efficacy and safety of pharmacologic therapies, such as Rho-kinase (ROCK) inhibitors, blood-derived products, growth factors, and regenerating agent on corneal cell regeneration. The promising results of these agents suggest that these can be viable options for corneal reconstruction and visual rehabilitation.
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Affiliation(s)
- Sang Beom Han
- Department of Ophthalmology, Kangwon National University Hospital, Kangwon National University, Chuncheon, Republic of Korea
| | - Yu-Chi Liu
- Singapore National Eye Centre, Singapore
- Singapore Eye Research Institute, Singapore
- Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Karim Mohamed-Noriega
- Department of Ophthalmology, Faculty of Medicine, University Hospital “Jose E. Gonzalez”, Autonomous University of Nuevo Leon, Monterrey, NL, Mexico
| | - Jodhbir S. Mehta
- Singapore National Eye Centre, Singapore
- Singapore Eye Research Institute, Singapore
- Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Ustaoglu M, Solmaz N, Onder F. Ocular surface chemical injury treated by regenerating agent (RGTA, Cacicol20). GMS OPHTHALMOLOGY CASES 2017; 7:Doc28. [PMID: 29082123 PMCID: PMC5655981 DOI: 10.3205/oc000079] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Objective: To present the successful outcome of regenerating agent (RGTA) treatment in a patient with severe ocular surface chemical injury. Methods: Case report Results: A 14-year-old female patient was admitted to our clinic following chemical burn in the left eye. Her best corrected visual acuity (BCVA) was 20/40; and she had total corneal and 75% conjunctival epithelial loss, corneal haze, and limbal ischemia for nine clock hours in the left eye. The patient had already received standard therapy consisting of patching, preservative-free artificial tears, topical netilmicin, topical dexamethasone, oral doxycycline, and vitamin C for two weeks. We initially cleaned the conjunctival necrotic tissues, applied the silicon hydrogel bandage contact lens, exchanged the topical netilmicin with preservative-free moxifloxacin and supplemented this therapy with RGTA (Cacicol20, Paris, France) once in two days. The BCVA of the patient improved to 20/20 and the ocular surface re-epithelization was completed on day 20. Conclusion: RGTAs are effective biological agents for the treatment of corneal epithelial defects following severe ocular surface chemical injuries.
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Affiliation(s)
- Melih Ustaoglu
- Sisli Hamidiye Etfal Training and Research Hospital, Ophthalmology Clinic, Istanbul, Turkey
| | - Nilgun Solmaz
- Haseki Training and Research Hospital, Ophthalmology Clinic, Istanbul, Turkey
| | - Feyza Onder
- Haseki Training and Research Hospital, Ophthalmology Clinic, Istanbul, Turkey
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41
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Treatment of acute ocular chemical burns. Surv Ophthalmol 2017; 63:214-235. [PMID: 28935121 DOI: 10.1016/j.survophthal.2017.09.005] [Citation(s) in RCA: 128] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Revised: 09/08/2017] [Accepted: 09/11/2017] [Indexed: 01/15/2023]
Abstract
Ocular chemical burns are an ophthalmic emergency and are responsible for 11.5%-22.1% of ocular injuries. Immediate copious irrigation is universally recommended in acute ocular burns to remove the offending agent and minimize damage. Conventional medical therapy consists of the use of agents that promote epithelialization, minimize inflammation, and prevent cicatricial complications. Biological fluids such as autologous serum, umbilical cord blood serum, platelet-rich plasma, and amniotic membrane suspension are a rich source of growth factors and promote healing when used as adjuncts to conventional therapy. Surgical treatment of acute ocular burns includes the debridement of the necrotic tissue, application of tissue adhesives, tenoplasty, and tectonic keratoplasty. Amniotic membrane transplantation is a novel surgical treatment that is increasingly being used as an adjunct to conventional treatment to promote epithelial healing, minimize pain, and restore visual acuity. Various experimental treatments that aim to promote wound healing and minimize inflammation are being evaluated such as human mesenchymal and adipose stem cells, beta-1,3 glucan, angiotensin-converting enzyme inhibitors, cultivated fibroblasts, zinc desferrioxamine, antifibrinolytic agents, antioxidants, collagen cross-linking, and inhibitors of corneal neovascularization.
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42
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Blood derived eye drops for the treatment of cornea and ocular surface diseases. Transfus Apher Sci 2017; 56:595-604. [DOI: 10.1016/j.transci.2017.07.023] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 07/26/2017] [Accepted: 07/30/2017] [Indexed: 12/30/2022]
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44
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Evidence-Based Update on Ocular Chemical Injuries. CURRENT OPHTHALMOLOGY REPORTS 2017. [DOI: 10.1007/s40135-017-0120-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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45
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Riestra AC, Alonso-Herreros JM, Merayo-Lloves J. Platelet rich plasma in ocular surface. ARCHIVOS DE LA SOCIEDAD ESPANOLA DE OFTALMOLOGIA 2016; 91:475-490. [PMID: 27062018 DOI: 10.1016/j.oftal.2016.03.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 02/28/2016] [Accepted: 03/01/2016] [Indexed: 06/05/2023]
Abstract
The use of platelet-rich preparations has experienced a significant increase in recent years due to its role in tissue-repair and regeneration. The aim of this study is to examine the available evidence regarding the application of plasma rich in growth factors, and its variations, on the ocular surface. A review is also presented on the effects of platelet-derived growth factors, the implications of the preparation methods, and the existing literature on the safety and efficacy of these therapies in ocular surface diseases. Despite the widespread use of platelet preparations there is no consensus on the most appropriate preparation method, and growth factors concentration vary with different systems. These preparations have been used in the treatment of ocular surface diseases, such as dry eye or persistent epithelial defects, among others, with good safety and efficacy profiles, but further studies are needed to compare to the currently available alternatives.
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Affiliation(s)
- A C Riestra
- Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, Oviedo, España.
| | | | - J Merayo-Lloves
- Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, Oviedo, España
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Baradaran-Rafii A, Eslani M, Haq Z, Shirzadeh E, Huvard MJ, Djalilian AR. Current and Upcoming Therapies for Ocular Surface Chemical Injuries. Ocul Surf 2016; 15:48-64. [PMID: 27650263 DOI: 10.1016/j.jtos.2016.09.002] [Citation(s) in RCA: 123] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Revised: 09/01/2016] [Accepted: 09/02/2016] [Indexed: 01/11/2023]
Abstract
Chemical injuries frequently result in vision loss, disfigurement, and challenging ocular surface complications. Acute interventions are directed at decreasing the extent of the injury, suppressing inflammation, and promoting ocular surface re-epithelialization. Chronically, management involves controlling inflammation along with rehabilitation and reconstruction of the ocular surface. Future therapies aimed at inhibiting neovascularization and promoting ocular surface regeneration should provide more effective treatment options for the management of ocular chemical injuries.
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Affiliation(s)
| | - Medi Eslani
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Zeeshan Haq
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Ebrahim Shirzadeh
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Michael J Huvard
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Ali R Djalilian
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
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Conway ED, Stiles J, Townsend WM, Weng HY. Comparison of the in vitro anticollagenase efficacy of homologous serum and plasma on degradation of corneas of cats, dogs, and horses. Am J Vet Res 2016; 77:627-33. [DOI: 10.2460/ajvr.77.6.627] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Suri K, Gong HK, Yuan C, Kaufman SC. Human Platelet Lysate as a Replacement for Fetal Bovine Serum in Limbal Stem Cell Therapy. Curr Eye Res 2016; 41:1266-1273. [PMID: 26863375 DOI: 10.3109/02713683.2015.1116586] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
PURPOSE To evaluate the use of human platelet lysate (HPL) as an alternative supplement for limbal explant culture. METHODS Culture media were prepared using either 10% pooled HPL (PHPL), single donor HPL, or fetal bovine serum (FBS). Limbal tissues, obtained from the Minnesota Lions Eye Bank, were cultured in each medium on plastic plates or on denuded amniotic membrane (AM). Immunofluorescence staining was performed for ABCG2, tumor protein p63α, and cytokeratin 3 (K3). Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate the expression of ABCG2 and p63. Limbal explants grown in each medium were labeled with bromodeoxyuridine (BrdU) to assess the proliferative capacity in each medium. Concentration of growth factors including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and platelet derived growth factor (PDGF) in HPL and PHPL was compared to that in human serum (HS). RESULTS Immunofluorescence staining on AM showed prominent expression of ABCG2, p63α but sparse expression of K3 in HPL and PHPL supplemented medium. Real time-PCR showed 1.7 fold higher expression of ABCG2 in PHPL supplemented medium (p = 0.03), and similar expression of p63 in HPL and PHPL supplemented medium compared to FBS medium. The proliferation assay showed that LSCs retained their proliferative potential in HPL supplemented medium. Higher concentration of growth factors were found in HPL, compared to HS. CONCLUSIONS Human platelet lysate has higher concentration of grown factors and is effective in maintaining growth and stem cell phenotype of corneal limbal explant cultures.
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Affiliation(s)
- Kunal Suri
- a Department of Ophthalmology , University of Minnesota , Minneapolis , MN , USA
| | - Hwee K Gong
- a Department of Ophthalmology , University of Minnesota , Minneapolis , MN , USA
| | - Ching Yuan
- a Department of Ophthalmology , University of Minnesota , Minneapolis , MN , USA
| | - Stephen C Kaufman
- a Department of Ophthalmology , University of Minnesota , Minneapolis , MN , USA.,b State University of New York-Downstate Medical Center , Brooklyn , NY , USA
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Management of androgenetic alopecia: a comparative clinical study between plasma rich in growth factors and topical minoxidil. EUROPEAN JOURNAL OF PLASTIC SURGERY 2016. [DOI: 10.1007/s00238-015-1175-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Anitua E, Muruzabal F, Tayebba A, Riestra A, Perez VL, Merayo-Lloves J, Orive G. Autologous serum and plasma rich in growth factors in ophthalmology: preclinical and clinical studies. Acta Ophthalmol 2015; 93:e605-14. [PMID: 25832910 DOI: 10.1111/aos.12710] [Citation(s) in RCA: 115] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Accepted: 02/06/2015] [Indexed: 01/22/2023]
Abstract
The use of blood derivatives represents an alternative therapeutic approach that is gaining interest in regenerative medicine due to its potential to stimulate and accelerate tissue healing. Autologous serum eye drops and platelet-enriched plasma eye drops are being used in the treatment of different ophthalmological disorders. In this review, we summarize the different blood-derived formulations used in the treatment and care of ocular surface disorders. The biological basis and use of autologous serum and plasma rich in growth factors are deeply evaluated as well as the challenges to be addressed in the future in this new generation of blood-derived therapies.
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Affiliation(s)
| | | | - Ali Tayebba
- Microbiology & Immunology; Walter G. Ross Chair in Ophthalmic Research; Ocular Surface Center; Bascom Palmer Eye Institute; University of Miami Miller School of Medicine; Miami Florida USA
| | - Ana Riestra
- Fernandez-Vega Ophthalmological Institute; Eye Research Foundation; University of Oviedo; Oviedo Spain
| | - Victor L. Perez
- Microbiology & Immunology; Walter G. Ross Chair in Ophthalmic Research; Ocular Surface Center; Bascom Palmer Eye Institute; University of Miami Miller School of Medicine; Miami Florida USA
| | - Jesus Merayo-Lloves
- Fernandez-Vega Ophthalmological Institute; Eye Research Foundation; University of Oviedo; Oviedo Spain
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